1. Field of the invention
This invention relates to a new glycopeptide antibiotic complex and to its production, recovery and separation into two bioactive components.
2. Description of the prior art
Although a number of glycopeptide antibiotics have been discovered, some of which are also effective in inhibiting the growth of tumors in lower animals and man, there remains a need for additional antimicrobial and antitumor agents. A brief summary of the more important glycopeptide antibiotics is provided below.
The bleomycins are water-soluble basic glycopeptides produced from Streptomyces verticillus. They were first discovered by Umezawa et al. in 1966 and reported in J. Antibiotics, 19A, 200 (1966); see also U.S. Pat. No. 3,681,491. The bleomycin complex has been separated into several components including bleomycin A, A.sub.1, A.sub.5 and B.sub.2. Bleomycin complex is presently being marketed for treatment of various neoplasms in man including squamous cell carcinoma, lymphosarcoma, reticulum cell sarcoma, testicular carcinoma and Hodgkin's disease.
The phleomycin group of antibiotics obtained from another strain of Streptomyces verticillus have been disclosed by Maeda et al. in J. Antibiotics: Vol. A9, pg. 82-85 (1956); Vol. A12, pg, 111 (1959); Vol. A12, pg. 285-289 (1959) and Vol. A17, pg. 194-199 (1964). As with bleomycin complex, phleomycin has been separated into a number of components which can exist in both a copper-free and a copper-complex form.
Zorbamycin and its related antibiotics zorbonomycin B and zorbonomycin C are reported in J. Antibiotics, 24(8), 543-557 (1971) and in British Pat. No. 1,277,150. These antibiotics isolated from fermentations of Streptomyces bikiniensis var. zorbonensis are closely related to the bleomycin and phleomycin families of antibiotics.
Another family of phleomycin-bleomycin group antibiotics was isolated from the culture broth of a variant of Streptomyces humidus and given the name YA-56. A description of the YA-56 complex and active components YA-56X and Y appears in J. Antibiotics, 24(10), 727-731 (1971) and in J. Antibiotics, 26, 77-83 (1973).
The antibiotic complex XK 49 and its main component victomycin (also called XK 49-1-B-2) are reported in J. Antibiotics, 28, 358-371 (1975). Victomycin was isolated from a sporangia-forming actinomycete, Streptosporangium violaceochromogenes MK 49 and appears to be similar to the bleomycins and zorbonomycin B.
The platomycins, a still further group of phleomycin-bleomycin-like antibiotics, were disclosed by Nara et al. in West German Published Application No. 2,408,121. Platomycin complex and its components platomycin A and B were produced from another strain of Streptosporangium designated Streptosporangium violaceochromogenes MK 78.